The present invention relates to biomedical testing of body fluids, to sensing device processing and fabrication, and more particularly to a method of fabricating a transdermal or interstitial fluid analyzer that integrates microneedles with micro-sensors with multiple integration layers and structures. The analyzer uses a specially fabricated applicator, patch, or carrier to communicate with a smart device, analyze the sensed data, and communicate the results to both patient and medical personnel.
Frequent testing for biological materials such as K+, Na+, Cl−ions, glucose, creatinine, cholesterol as well as therapeutic agents such as drugs used in the treatment of cardiovascular, renal, neurological, oncological, and other medical conditions is often required for the effective treatment and monitoring of patients. The standard of care involves blood extraction in a clinical setting with subsequent serum analysis for the concentrations of one or more electrolytes or other biological or therapeutic molecules of interest.
This testing process results in high costs related to performing the blood or fluid extraction in a clinical setting, delays of hours to days related to the testing frequently being done by specialized personnel or laboratories, and inconvenience to the patient related to travel to the medical facility and the significant time required. As a result, testing is often performed at suboptimal frequency and risks a delayed response to a medically significant event.
The use of microneedles that can perforate the stratum corneum (the outer layer of the epidermis) and reach the transdermal fluid under the skin is part of the existing state of the art. When made hollow, the microneedles provide access to the interstitial fluid among subcutaneous cells and permit the delivery of drugs or access to the interstitial fluid for analysis. Microneedles have been made from a large variety of materials, from metals to ceramics to polymers to silicon, with varying degrees of performance and process control. While these microneedles can access the transdermal region, when manufactured to the correct dimensions, they are not deep enough to reach the blood capillaries or nerve endings. Their application is therefore practically painless and does not produce bleeding.
Research in the use of microneedles has focused mostly on methods for delivering drugs into the subcutaneous region. Separately, sensors using specially formulated biochemical films to obtain electrical readings and transistors fabricated in semiconductors such as silicon, modified to be sensitive and specific for ions such as K+have also been occasionally described. Key difficulties with existing approaches are the lack of sufficient process control to achieve medical grade devices and complex integration methods that are not best suited for the high volume manufacturing necessary to achieve large volumes and low cost. As a result, to the best knowledge of the inventors, practical devices that allow routine testing of transdermal fluid at low cost by non-specialized personnel are not available in the marketplace.
The following patents and publications relate to the field of the invention.
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